Progress in the Study of Colorectal Cancer Caused by Altered Gut Microbiota After Cholecystectomy

Ma, Yanpeng; Qu, Ruize; Zhang, Yi; Jiang, Changtao; Zhang, Zhipeng; Fu, Wei

doi:10.3389/fendo.2022.815999

Cited by 11 publications

(9 citation statements)

References 100 publications

(134 reference statements)

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“…Until now, it is widely shown that PC patients have a higher risk of gastrointestinal complications, but no increased risk of IBD in PC patients has been reported in limited studies, and the mechanism was also not clearly underlined in animals. 4 , 5 In our present time-course study, we have shown that cholecystectomy, after a relatively longer duration of post-operation, ameliorated DSS-induced colitis in mice, in keeping with our published research suggested that the follow-up period was a pivotal factor for clinical outcomes in PC patients. 17 Based on decades-long duration in the PC patients, further studies are needed a markedly long follow-up year to clarify the role of duration after cholecystectomy in IBD patients.…”

Section: Discussionsupporting

confidence: 91%

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Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment

Liu

Ren

et al. 2022

Gut Microbes

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Although post-cholecystectomy (PC) patients usually have gastrointestinal complications and a higher risk of colorectal cancer, previous studies undetected a heightened risk of inflammatory bowel disease. Thus, we tried to investigate cholecystectomy’s impact and pathophysiological mechanism on murine colitis models and clarify the association among fecal bile acids (BAs), mucosal bacterial microbiota, and immune cells in the PC patients. One month or three months after cholecystectomy, mice have induced colitis and tested BAs and fecal microbiota analysis. Next, mice were treated with various cholecystectomy-accumulated bile acids in drinking water for three months before inducing colitis. All 14 paired PC patients and healthy subjects were enrolled for BAs and mucosal microbiota analysis. Cholecystectomy ameliorated DSS-induced murine colitis, accelerated mucosal repair, and induced a significant shifting of fecal microbiota and BAs profiles under colitis status, which featured a higher relative abundance of species involved in BAs metabolism and increased secondary BAs concentrations. Cholecystectomy-associated secondary BAs (LCA, DCA, and HDCA) also ameliorated DSS-induced colitis and accelerated mucosal repair in mice. Cholecystectomy and specific secondary BAs treatments inhibited monocytes/macrophages recruitment in colitis mice. In vitro , cholecystectomy-associated secondary BAs also downregulated monocytes chemokines in the THP-1 derived macrophages through activation of the LXRα-linked signaling pathway. The alterations of mucosal microbiota and fecal BAs profiles were found in the PC patients, characterized as increased species with potential immuno-modulating effects and secondary BAs, which were negatively associated with peripheral monocytes levels. Cholecystectomy-induced secondary bile acids accumulation ameliorated colitis through inhibiting monocyte/macrophage recruitment, which might be mediated by the LXRα-related signaling pathway. Cholecystectomy, after 3 months follow-up, has an immune-regulatory role in murine colitis, preliminarily explaining that no increased risk of IBD had been reported in the PC patients, which still warrants further studies.

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Section: Discussionsupporting

confidence: 91%

“… 2 , 3 Cholecystectomy also induced intestinal bacterial and bile acids dysbiosis. 4 , 5 Even so, few studies reported the association between cholecystectomy and IBD. In a population-based cohort study, the risk of IBD did not change significantly between the PC patients and healthy controls (0.062% vs 0.051%).…”

Section: Introductionmentioning

confidence: 99%

Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment

Liu

Ren

et al. 2022

Gut Microbes

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“…And its impact on health is still unclear. Deoxycholic acid (DCA) and some pathogenic bacteria are considered to be tumorigenic [12,22]. Previous study has suggested that secondary bile acids concentration were higher in the right colon [23] and an increased rate of right CRC after cholecystectomy was also observed [4,9,20].…”

Section: Discussionmentioning

confidence: 99%

Alteration of Ascending Colon Mucosal Microbiota in Patients after Cholecystectomy

Fan

Lü

Cui

et al. 2023

Preprint

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BACKGROUND Cholecystectomy is an effective therapy for gallstones, however, the incidence of CRC has increased significantly in post-cholecystectomy (PC) patients. Whether it is related to the changed mucosal microbiota in ascending colon is still unclear. AIM To explore the association between gut microbiota and cholecystectomy. METHODS Mucosal biopsy samples were collected from 30 PC patients (the test group) with gallbladder stones and 28 healthy individuals (the control group) by colonoscopy. Subsequently, the test group was subdivided into the YMA group or SNR group(age over or under 60), DG group or NG group (with or without diarrhea) and Log group or Sht group(duration over or under 5 years) according to patients’ clinical characteristics. 16S-rRNA gene amplicon sequencing was performed and alpha diversity, beta diversity and composition analysis were determined. The Phylogenetic Investigation of Communities by Reconstruction of Unobserved States based on the Kyoto Encyclopedia of Genes and Genomes database was used to predict the function of the microbiome. RESULTS The PC patients showed similar richness and overall composition with healthy controls, but PC patients over 60 years showed a different structure than those under 60 years. At the phylum level, the richness of Bacteroidetes was significantly higher in PC patients. Similarly, the genus Bacteroides, Parabacteroidesand Bilophila were remarkably more abundant in PC patients compared with the controls. In addition, the PC patients had significant enrichments in both metabolic pathways, including Lipopolysaccharide and vancomycin group antibiotics biosynthesis compared to the controls. CONCLUSION Our study suggested that mucosal microbiota was changed in PC patients, which may reveal new insight into therapeutic options for colorectal cancer and diarrhea after cholecystectomy.

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“…In individuals who have undergone cholecystectomy (CC), there is evidence of increased production of secondary BAs, a phenomenon documented in both experimental and clinical studies [ 11 , 23 ]. Additionally, with specific reference to deoxycholic acid (DCA), an increased incidence of certain types of cancer has been observed in patients who have undergone cholecystectomy [ 24 ]. It has been suggested that DCA possesses carcinogenic and mutagenic properties, and there is also evidence indicating that DCA itself can contribute to gut dysbiosis [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

Deoxycholic Acid, a Secondary Bile Acid, Increases Cardiac Output and Blood Pressure in Rats

Nowiński,

Chabowski,

Giebułtowicz

et al. 2023

Nutrients

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Background: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Elevated serum concentrations of DCA are observed in cardiovascular disease (CVD). We hypothesized that DCA might influence hemodynamic parameters in rats. Methods: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3–4-month-old Sprague–Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. Results: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/L. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds—prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor)—significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. Conclusions: DCA elevates BP primarily by augmenting cardiac output. As a metabolite derived from gut bacteria, DCA potentially serves as a mediator in the interaction between the gut microbiota and the host’s circulatory system.

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Progress in the Study of Colorectal Cancer Caused by Altered Gut Microbiota After Cholecystectomy

Cited by 11 publications

References 100 publications

Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment

Cholecystectomy-induced secondary bile acids accumulation ameliorates colitis through inhibiting monocyte/macrophage recruitment

Alteration of Ascending Colon Mucosal Microbiota in Patients after Cholecystectomy

Deoxycholic Acid, a Secondary Bile Acid, Increases Cardiac Output and Blood Pressure in Rats

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